Mochizuki Kasumi, Mitova Violeta, Makino Kimiko, Terada Hiroshi, Takeuchi Issei, Troev Kolio
Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641, Yamazaki, Noda 278-8510, Chiba, Japan.
Institute of Polymers, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.
Int J Mol Sci. 2024 Apr 20;25(8):4518. doi: 10.3390/ijms25084518.
pH-sensitive amphiphilic diblock polyphosphoesters containing lactic acid units were synthesized by multistep one-pot polycondensation reactions. They comprise acid-labile P(O)-O-C and C(O)-O-C bonds, the cleavage of which depends on the pH of the medium. The structure of these copolymers was characterized by H, C {H}, P NMR, and size exclusion chromatography (SEC). The newly synthesized polymers self-assembled into the micellar structure in an aqueous solution. The effects of the molecular weight of the copolymer and the length of the hydrophobic chain on micelle formation and stabilityand micelle size were studied via dynamic light scattering (DLS). Drug loading and encapsulation efficiency tests using doxorubicin revealed that hydrophobic drugs can be delivered by copolymers. It was established that the molecular weight of the copolymer, length of the hydrophobic chain and content of lactate units affects the size of the micelles, drug loading, and efficiency of encapsulation. A copolymer with 10.7% lactate content has drug loading (3.2 ± 0.3) and efficiency of encapsulation (57.4 ± 3.2), compared to the same copolymer with 41.8% lactate content (1.63%) and (45.8%), respectively. It was demonstrated that the poly[alkylpoly(ethylene glycol) phosphate--alkylpoly(ethylene glycol)lactate phosphate] DOX system has a pH-sensitive response capability in the result in which DOX was selectively accumulated into the tumor, where pH is acidic. The results obtained indicate that amphiphilic diblock polyphosphoesters have potential as drug carriers.
通过多步一锅法缩聚反应合成了含乳酸单元的pH敏感两亲性二嵌段聚磷酸酯。它们包含酸不稳定的P（O）-O-C和C（O）-O-C键，其断裂取决于介质的pH值。这些共聚物的结构通过H、C{H}、P NMR和尺寸排阻色谱（SEC）进行了表征。新合成的聚合物在水溶液中自组装成胶束结构。通过动态光散射（DLS）研究了共聚物分子量和疏水链长度对胶束形成、稳定性以及胶束尺寸的影响。使用阿霉素进行的载药和包封效率测试表明，疏水药物可由共聚物递送。已确定共聚物的分子量、疏水链长度和乳酸酯单元含量会影响胶束尺寸、载药量和包封效率。乳酸酯含量为10.7%的共聚物的载药量为（3.2±0.3），包封效率为（57.4±3.2），而乳酸酯含量为41.8%的相同共聚物的载药量和包封效率分别为（1.63%）和（45.8%）。结果表明，聚[烷基聚（乙二醇）磷酸酯-烷基聚（乙二醇）乳酸酯磷酸酯]阿霉素系统在阿霉素选择性积聚到酸性pH值的肿瘤中的结果中具有pH敏感响应能力。所得结果表明两亲性二嵌段聚磷酸酯具有作为药物载体的潜力。
